Acting FDA Commissioner Janet Woodcock, in a letter to HHS' Office of the Inspector General (OIG) on Friday, called for an investigation into the approval process of Aduhelm, a new drug for Alzheimer's disease that has spurred controversy since its approval in June.

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Background

Aducanumab, which is sold under the brand name Aduhelm and made by Biogen, attacks the beta-amyloid proteins associated with Alzheimer's disease.

To seek FDA approval of Aduhelm, Biogen launched two Phase 3 randomized controlled clinical trials of the drug—but the trials were halted in March 2019 after independent monitors determined the drug was unlikely to benefit patients.

However, in October 2019, Biogen announced that it had conducted a new analysis of data from the trials. According to the updated analysis, a high dose of Aduhelm in one trial showed a small benefit in slowing cognitive decline, and in both trials Aduhelm was effective at removing beta-amyloid proteins.

Biogen submitted its analysis of the Phase 3 trials to seek FDA approval for the drug. Late last year, a panel of independent experts convened by FDA looked at Biogen's data. They determined there was not enough evidence to suggest the treatment had a significant benefit for patients, and they argued the drug should not be approved.

However, FDA is not obliged to follow the panel's recommendations. On June 7, it announced the decision to approve Aduhelm on a conditional basis—saying Biogen must still conduct a large clinical trial to confirm that removing beta-amyloid proteins actually leads to cognitive benefits for patients.

But earlier this month, FDA revised its approval for the drug. FDA narrowed its previous recommendation that the drug be available to all Alzheimer's patients to now making it available only to Alzheimer's patients with early-stage symptoms of the disease. In addition, if the future trial fails, FDA could rescind the drug's approval entirely.

Acting FDA Commissioner calls for investigation into approval process

In the letter to OIG, Woodcock said while she had "tremendous confidence in the integrity" of the FDA team that reviewed Aduhelm, she wanted to address concerns about several meetings Biogen officials had with FDA officials prior to the drug's approval that "may have occurred outside of the formal correspondence process."

According to the New York Times, Biogen executives met informally with FDA officials prior to restarting the discussions that ultimately led to the drug's approval. In addition, over the course of the summer of 2020, representatives from Biogen and FDA collaboratively reviewed the data from Biogen's studies, the Times reports, citing a STAT News investigation.

According to the Times, it is not unusual for drug company executives to have informal meetings with FDA officials. However, it is unusual for drug companies to share data or information in those meetings that would otherwise be shared in formal FDA applications or reviews.

Woodcock wrote, "To the extent these concerns could undermine the public's confidence in FDA's decision, I believe it is critical that the events at issue be reviewed by an independent body such as [OIG] in order to determine whether any interactions that occurred between Biogen and FDA review staff were inconsistent with FDA policies and procedures."

In a statement, a Biogen spokesperson said the company will "cooperate with any inquiry in connection with a possible review of the regulatory process."

According to STAT News, OIG—which operates independently of any federal agency—does not have to comply with Woodcock's request. However, Tesia Williams, a spokesperson for OIG, said the office has "received the letter and [is] reviewing it for appropriate action."

Woodcock's letter comes after Rep. Carolyn Maloney (D-N.Y.), chair of the House Committee on Oversight and Reform, and Rep. Frank Pallone (D-N.J.), chair of the House Committee on Energy and Commerce, in a statement said they have "serious concerns" about the price and approval process of Aduhelm, and said both committees would investigate. (Howard, CNN, 6/29; Robbins, New York Times, 7/9; Foley, Politico, 7/9; Garde et. al., STAT News, 7/9; McGinley, Washington Post, 7/9; Burton, Wall Street Journal, 7/9; Mishra, Reuters, 7/9)